Tag: long covid vs ME/CFS

Assessing the Relationship in Symptomology of Myalgic Encephalitis/Chronic Fatigue Syndrome and Long COVID

Abstract:

The symptomology of Myalgic Encephalitis/Chronic Fatigue Syndrome (ME/CFS) shares many commonalities with Long COVID (LC). This study aimed to clearly define the comparison between ME/CFS and LC in terms of symptomology.

A cross-sectional analysis of 27,651 interviewees from a National Health Interview Survey 2022 adult dataset was conducted. The data was controlled for subject’s sex, race/ethnicity, age, life satisfaction, insurance coverage, poverty ratio, and comorbidities. A logistic regression was used to compare four groups: (1) LC individuals, (2) ME/CFS individuals, (3) LC with ME/CFS individuals, and (4) controls by symptoms of depression, anxiety, physical activity, fatigue, and memory.

The results showed that subjects with both ME/CFS and LC were more likely to report memory issues, anxiety, depression, fatigue, and difficulty with physical activity followed by subjects with ME/CFS only, LC only, and the controls (P < .01).

Our study suggests a synergistic mechanism between ME/CFS and LC in developing issues with anxiety, depression, fatigue, and physically activity in patients. The study’s conclusions highlight the need to elucidate the possible overlap in pathophysiological mechanisms of ME/CFS and LC in the symptomology of patients.

Source: Garapaty N, Reyes KM, Tehrani L, Mendoza MB, Hardigan P. Assessing the Relationship in Symptomology of Myalgic Encephalitis/Chronic Fatigue Syndrome and Long COVID. Am J Med Open. 2025 Feb 1;13:100085. doi: 10.1016/j.ajmo.2024.100085. PMID: 40271015; PMCID: PMC12017839. https://pmc.ncbi.nlm.nih.gov/articles/PMC12017839/ (Full text)

Autoantibody targeting therapies in post COVID syndrome and myalgic encephalomyelitis/chronic fatigue syndrome

Introduction:

Following the shift of SARS-CoV-2 from pandemic to endemic, post COVID syndrome (PCS) joins the list of already known post-acute infection syndromes (PAIS) and its most severe manifestation, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The exact pathomechanism of PCS has not yet been fully understood. Immune dysregulation with persistent inflammation, microvascular injury with endothelial dysfunction, autonomic nervous system dysfunction, mitochondrial dysfunction, gut microbiome dysbiosis and persistence of SARS-CoV-2 virus or SARS-CoV-2 viral particles have been proposed [1].

Autoimmunity could be a linking element across various mechanisms and there is indeed mounting evidence that autoantibodies (AAbs) in particular play a role in a subset of PCS and ME/CFS. In ME/CFS there are now numerous studies showing elevated levels and altered functions of G-protein coupled receptor autoantibodies (GPCR AAbs) and their correlation with severity of key symptoms [2]. First trials with AAb-targeting therapies show promising though mixed results. These include studies directly targeting AAbs by removal with immunoadsorption or their enhanced degradation with efgartigimod or neutralization with BC007 (rovunaptabin). Further B cell depletion with rituximab or plasma cell depletion with daratumumab has yielded some positive but inconsistent results.

Source: Wohlrab F, Eltity M, Ufer F, Paul F, Scheibenbogen C, Bellmann-Strobl J. Autoantibody targeting therapies in post COVID syndrome and myalgic encephalomyelitis/chronic fatigue syndrome. Expert Opin Biol Ther. 2025 Apr 10. doi: 10.1080/14712598.2025.2492774. Epub ahead of print. PMID: 40211686. https://www.tandfonline.com/doi/full/10.1080/14712598.2025.2492774#d1e211 (Full text)

Identifying commonalities and differences between EHR representations of PASC and ME/CFS in the RECOVER EHR cohort

Abstract:

Background: Shared symptoms and biological abnormalities between post-acute sequelae of SARS-CoV-2 infection (PASC) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) could suggest common pathophysiological bases and would support coordinated treatment efforts. Empirical studies comparing these syndromes are needed to better understand their commonalities and differences.

Methods: We analyzed electronic health record data from 6.5 million adult patients from the National COVID Cohort Collaborative. PASC and ME/CFS diagnostic groups were defined based on recorded diagnoses, and other recorded conditions within the two groups were used to train separate machine learning-driven computable phenotypes (CPs). The most predictive conditions for each CP were examined and compared, and the overlap of patients labeled by each CP was examined. Condition records from the diagnostic groups were also used to statistically derive condition clusters. Rates of subphenotypes based on these clusters were compared between PASC and ME/CFS groups.

Results: Approximately half of patients labeled by one CP are also labeled by the other. Dyspnea, fatigue, and cognitive impairment are the most-predictive conditions shared by both CPs, whereas other most-predictive conditions are specific to one CP. Recorded conditions separate into cardiopulmonary, neurological, and comorbidity clusters, with the cardiopulmonary cluster showing partial specificity for the PASC groups.

Conclusions: Data-driven approaches indicate substantial overlap in the condition records associated with PASC and ME/CFS diagnoses. Nevertheless, cardiopulmonary conditions are somewhat more commonly associated with PASC diagnosis, whereas other conditions, such as pain and sleep disturbances, are more associated with ME/CFS diagnosis. These findings suggest that symptom management approaches to these illnesses could overlap.

Source: Powers JP, McIntee TJ, Bhatia A, Madlock-Brown CR, Seltzer J, Sekar A, Jain N, Hornig M, Seibert E, Leese PJ, Haendel M, Moffitt R, Pfaff ER; N3C Consortium and RECOVER-EHR. Identifying commonalities and differences between EHR representations of PASC and ME/CFS in the RECOVER EHR cohort. Commun Med (Lond). 2025 Apr 11;5(1):109. doi: 10.1038/s43856-025-00827-5. PMID: 40210986. https://www.nature.com/articles/s43856-025-00827-5 (Full text)

Understanding symptom clusters, diagnosis and healthcare experiences in myalgic encephalomyelitis/chronic fatigue syndrome and long COVID: a cross-sectional survey in the UK

Abstract:

Objectives: This study aims to provide an in-depth analysis of the symptoms, coexisting conditions and service utilisation among people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID. The major research questions include the clustering of symptoms, the relationship between key factors and diagnosis time, and the perceived impact of National Institute for Health and Care Excellence (NICE) guidelines on patient care.

Design: Cross-sectional survey using secondary data analysis.

Setting: Community-based primary care level across the UK, incorporating online survey participation.

Participants: A total of 10 458 individuals responded to the survey, of which 8804 confirmed that they or a close friend/family member had ME/CFS or long COVID. The majority of respondents were female (83.4%), with participants from diverse regions of the UK.

Primary and secondary outcome measures: Primary outcomes included prevalence and clustering of symptoms, time to diagnosis, and participant satisfaction with National Health Service (NHS) care, while secondary outcomes focused on symptom management strategies and the perceived effect of NICE guidelines.

Results: Fatigue (88.2%), postexertional malaise (78.2%), cognitive dysfunction (88.4%), pain (87.6%) and sleep disturbances (88.2%) were the most commonly reported symptoms among participants with ME/CFS, with similar patterns observed in long COVID. Time to diagnosis for ME/CFS ranged widely, with 22.1% diagnosed within 1-2 years of symptom onset and 12.9% taking more than 10 years. Despite updated NICE guidelines, only 10.1% of participants reported a positive impact on care, and satisfaction with NHS services remained low (6.9% for ME/CFS and 14.4% for long COVID).

Conclusions: ME/CFS and long COVID share overlapping but distinct symptom clusters, indicating common challenges in management. The findings highlight significant delays in diagnosis and low satisfaction with specialist services, suggesting a need for improved self-management resources and better-coordinated care across the NHS.

Source: Mansoubi M, Richards T, Ainsworth-Wells M, Fleming R, Leveridge P, Shepherd C, Dawes H. Understanding symptom clusters, diagnosis and healthcare experiences in myalgic encephalomyelitis/chronic fatigue syndrome and long COVID: a cross-sectional survey in the UK. BMJ Open. 2025 Apr 2;15(4):e094658. doi: 10.1136/bmjopen-2024-094658. PMID: 40180399. https://bmjopen.bmj.com/content/15/4/e094658 (Full text)

An In-Depth Exploration of the Autoantibody Immune Profile in ME/CFS Using Novel Antigen Profiling Techniques

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disorder characterized by serious physical and cognitive impairments. Recent research underscores the role of immune dysfunction, including the role of autoantibodies, in ME/CFS pathophysiology.

Expanding on previous studies, we analyzed 7542 antibody-antigen interactions in ME/CFS patients using two advanced platforms: a 1134 autoantibody Luminex panel from Oncimmune and Augmenta Bioworks, along with Rapid Extracellular Antigen Profiling (REAP), a validated high-throughput method that measures autoantibody reactivity against 6183 extracellular human proteins and 225 human viral pathogen proteins.

Unlike earlier reports, our analysis of 172 participants revealed no significant differences in autoantibody reactivities between ME/CFS patients and controls, including against GPCRs such as β-adrenergic receptors. However, subtle trends in autoantibody ratios between male and female ME/CFS subgroups, along with patterns of herpesvirus reactivation, suggest the need for broader and more detailed exploration.

Source: Germain A, Jaycox JR, Emig CJ, Ring AM, Hanson MR. An In-Depth Exploration of the Autoantibody Immune Profile in ME/CFS Using Novel Antigen Profiling Techniques. Int J Mol Sci. 2025 Mar 20;26(6):2799. doi: 10.3390/ijms26062799. PMID: 40141440; PMCID: PMC11943395. https://pmc.ncbi.nlm.nih.gov/articles/PMC11943395/ (Full text)

Cognitive Impairments in Two Samples of Individuals with ME/CFS and Long COVID: A Comparative Analysis

Abstract:

Cognitive impairments, including memory and concentration difficulties, are common in individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID. These conditions frequently co-occur, but it remains unclear how cognitive difficulties differ between individuals with ME/CFS, long COVID, both, or neither. The purpose of this study was to examine cognitive impairment presence and type for individuals with and without these conditions.

Data from the 2022 and 2023 National Health Interview Survey were analyzed. Participants included 27,512 and 29,404 U.S. adults in 2022 and 2023, respectively. Survey weights and variance estimation variables were utilized and multivariate logistic regression models assessed the likelihood of cognitive difficulty, accounting for sociodemographics and shared variance. Participants from both cohorts were primarily female, white, and non-Hispanic/Latine, with an average age of 48.1 years in both cohorts.

ME/CFS (aOR 6.18; 95% CI 4.82-7.93; aOR 5.33; 95% CI 4.04-7.05) and long COVID (aOR 2.01; 95% CI 1.67-2.44; aOR 2.16; 95% CI 1.82-2.56) were significantly associated with reported cognitive difficulties, after controlling for the other condition and sociodemographic factors. Individuals with ME/CFS, particularly those with comorbid long COVID, are especially prone to memory and concentration difficulties.

Source: Sirotiak Z, Adamowicz JL, Thomas EBK. Cognitive Impairments in Two Samples of Individuals with ME/CFS and Long COVID: A Comparative Analysis. J Clin Psychol Med Settings. 2025 Mar 22. doi: 10.1007/s10880-025-10074-4. Epub ahead of print. PMID: 40120036. https://pubmed.ncbi.nlm.nih.gov/40120036/

Predisposing and Precipitating Factors in Epstein–Barr Virus-Caused Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Long COVID following SARS-CoV-2 and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) following infectious mononucleosis (IM) are two examples of post-viral syndromes. The identification of risk factors predisposing patients to developing and maintaining post-infectious syndromes may help uncover their underlying mechanisms.
The majority of patients with ME/CFS report infectious illnesses before the onset of ME/CFS, with 30% of cases of ME/CFS due to IM caused by the Epstein–Barr virus. After developing IM, one study found 11% of adults had ME/CFS at 6 months and 9% had ME/CFS at 1 year. Another study of adolescents found 13% and 7% with ME/CFS at 6 and 12 months following IM, respectively. However, it is unclear which variables are potential risk factors contributing to the development and maintenance of ME/CFS following IM, because few prospective studies have collected baseline data before the onset of the triggering illness.
The current article provides an overview of a study that included pre-illness predictors of ME/CFS development following IM in a diverse group of college students who were enrolled before the onset of IM. Our data set included an ethnically and sociodemographically diverse group of young adult students, and we were able to longitudinally follow these youths over time to better understand the risk factors associated with the pathophysiology of ME/CFS.
General screens of health and psychological well-being, as well as blood samples, were obtained at three stages of the study (Stage 1—Baseline—when the students were well, at least 6 weeks before the student developed IM; Stage 2—within 6 weeks following the diagnosis of IM, and Stage 3—six months after IM, when they had either developed ME/CFS or recovered). We focused on the risk factors for new cases of ME/CFS following IM and found factors both at baseline (Stage 1) and at the time of IM (Stage 2) that predicted nonrecovery. We are now collecting seven-year follow-up data on this sample, as well as including cases of long COVID. The lessons learned in this prospective study are reviewed.
Source: Jason LA, Katz BZ. Predisposing and Precipitating Factors in Epstein–Barr Virus-Caused Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Microorganisms. 2025; 13(4):702. https://doi.org/10.3390/microorganisms13040702 https://www.mdpi.com/2076-2607/13/4/702 (Full text)

Efficacy of vitamin D replacement therapy on 28 cases of myalgic encephalomyelitis/chronic fatigue syndrome after COVID-19 vaccination

Abstract:

Background: Prolonged symptoms have been reported following both COVID-19 infection and vaccination, with some cases leading to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Of 80 patients presenting to our hospital with postvaccination syndrome, 28 met the diagnostic criteria for ME/CFS. We conducted a retrospective study on these 28 patients.

Methods: We measured serum 25-hydroxyvitamin D levels in 28 patients who developed ME/CFS after COVID-19 vaccination between August 2022 and February 2024. Vitamin D replacement therapy included dietary counseling, sun exposure recommendations, and oral vitamin D supplementation. We evaluated changes in blood vitamin D levels and symptom improvement.

Results: At initial visit, 27 of 28 patients diagnosed with ME/CFS had insufficient or deficient serum 25-hydroxyvitamin D levels (16 ± 4 ng/mL, mean ± SD). Following vitamin D replacement therapy, we observed an increase in blood vitamin D levels (28 ± 5 ng/mL) associated with a decrease in ME/CFS diagnostic symptoms (from 10.3 ± 2.1 to 3.3 ± 2.0). Notably, 23 of 28 patients (82%) no longer met ME/CFS diagnostic criteria after the therapy. Among the symptoms, sleep problems showed the most improvement (71%), followed by autonomic symptoms (68%).

Conclusions: For patients developing ME/CFS after COVID-19 vaccination with insufficient or deficient vitamin D levels, appropriate vitamin D replacement therapy under medical guidance may lead to symptomatic relief. We are preparing a randomized controlled trial to evaluate the efficacy of vitamin D replacement therapy in individuals with ME/CFS who have developed vitamin D deficiency following COVID-19 infection or vaccination.

Source: Kodama S, Konishi N, Hirai Y, Fujisawa A, Nakata M, Teramukai S, Fukushima M. Efficacy of vitamin D replacement therapy on 28 cases of myalgic encephalomyelitis/chronic fatigue syndrome after COVID-19 vaccination. Nutrition. 2025 Feb 18;134:112718. doi: 10.1016/j.nut.2025.112718. Epub ahead of print. PMID: 40090177. https://www.sciencedirect.com/science/article/pii/S089990072500036X (Full text)

Health-related quality of life in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Post COVID-19 Condition: a systematic review

Abstract:

Purpose: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Post COVID-19 Condition (PCC) are debilitating, chronic multi-systemic illnesses that require multidisciplinary care. However, people with ME/CFS (pwME/CFS) and people with PCC (pwPCC) are often precluded from accessing necessary disability and social support services. These unmet care needs exacerbate the existing illness burdens experienced by pwME/CFS and pwPCC. To deliver appropriate care and optimise health outcomes for pwME/CFS and pwPCC, the development of evidence-based healthcare policies that recognise the disabling impacts of these illnesses must be prioritised. This systematic review summarises the health-related quality of life (HRQoL) of pwME/CFS and pwPCC when compared with healthy controls (HCs) to elucidate the impacts of these illnesses and guide healthcare policy reform.

Methods: CINAHL, Embase, MEDLINE, PubMed, PsycINFO and the Web of Science Core Collection were systematically searched from 1st January 2003 to 23rd July 2024. Eligible publications included observational studies capturing quantitative HRQoL data among pwME/CFS or pwPCC when compared with HCs. The use of validated patient-reported outcome measures (PROMs) was mandatory. Eligible studies were also required to employ the most stringent diagnostic criteria currently available, including the Canadian Consensus Criteria or International Consensus Criteria for ME/CFS and the World Health Organization case definition for PCC (PROSPERO ID: CRD42024501309).

Results: This review captured 16 studies, including eight studies among pwME/CFS, seven studies among pwPCC and one study among both illness cohorts. Most participants were female and middle-aged. All pwPCC had experienced prolonged COVID-19 symptoms for at least three months. When compared with HCs, all HRQoL domains were significantly impaired among pwME/CFS and pwPCC. Both illnesses had a salient impact on physical health, including pain and ability to perform daily and work activities. While direct comparisons between pwME/CFS and pwPCC were limited by inconsistencies in the PROMs employed, comparable impact trends across HRQoL domain scores were observed.

Conclusion: ME/CFS and PCC have similar, profound impacts on HRQoL that warrant access to multidisciplinary disability and social support services. Future research must harmonise HRQoL data collection and prioritise longitudinal investigations among pwME/CFS and pwPCC to characterise PCC subgroups (including those fulfilling ME/CFS criteria) and predictors of prognosis.

Source: Weigel B, Inderyas M, Eaton-Fitch N, Thapaliya K, Marshall-Gradisnik S. Health-related quality of life in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Post COVID-19 Condition: a systematic review. J Transl Med. 2025 Mar 13;23(1):318. doi: 10.1186/s12967-025-06131-z. PMID: 40075382. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-025-06131-z (Full text)

Post-infective myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and post-COVID as two puzzling faces of the same medal. Recent insights

Background:

How much is truly shared in terms of pathogenesis, symptomatology, and disease progression between the myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and post-COVID, and why have these two very complex conditions recently been grouped under the same umbrella terms?
The 1st International Conference on Clinical and Scientific Advances of ME/CFS/long COVID”, held in Portugal, on April 3rd and 4th 2024 [1], addressed, for the first time, this concern, shedding light onto two highly…
Source: Chirumbolo S, Franzini M, Tirelli U. Post-infective myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and post-COVID as two puzzling faces of the same medal. Recent insights. Int Immunopharmacol. 2025 Mar 7:114365. doi: 10.1016/j.intimp.2025.114365. Epub ahead of print. PMID: 40057420. https://www.sciencedirect.com/science/article/abs/pii/S1567576925003558